FDA Approval Sought for Selinexor for Treatment of Patients With Relapsed or Refractory DLBCL

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Positive results from the phase IIb SADAL study presented at the International Conference on Malignant Lymphoma were the reason for the NDA. The most recently reported data showed that selinexor produced a 28.3% overall response rate (ORR) and an 11.8% complete response (CR) rate as a single agent for treatment of patients with relapsed or refractory DLBCL. The median duration of response was 9 months.

According to data previously reported at the 2018 American Society of Hematology (ASH) Annual Meeting, the median overall survival (OS) in all study participants was 9.1 months at the time of analysis.²

“These data highlight Xpovio’s potential as a new, first-in-class oral therapy for patients whose DLBCL has progressed following 2 prior treatments and who have extremely limited treatment options available. The submission of this second NDA is a significant achievement for Karyopharm and brings Xpovio 1 step closer to serving an entirely new group of patients,” said Sharon Shacham, PhD, MBA, founder, president, and chief scientific officer of Karyopharm.

The multicenter, open-label study has enrolled 130 patients to assess the objective responses with selinexor administered at 60 mg doses orally, twice weekly on days 1 and 3 for 28 days. The objective responses are assessed per revised response criteria in the Guidelines of the International Working Group.

Adult aged 18 years or older are eligible to enroll in the study granted they have an ECOG performance status ≤2, a pathologically confirmed de novo DLBCL, objective and documented evidence of disease progression, prior treatment with at least 2 but no more than 5 prior systemic therapy regimens for DLBCL, measurable disease, and at least 60 days between partial responses or CRs on prior anti-DLBCL therapy.

The study excludes individuals with DLBCL with mucosa-associated lymphoid tissue, composite lymphoma, or DLBCL transformed from diseases other than indolent non-Hodgkin Lymphoma. Primary mediastinal large B-cell lymphoma, known central nervous system lymphoma, active hepatitis B or C infections, and known HIV infection were also among the exclusion criterion.

Previously, data presented at the ASH  2018 led toa Fast Track designationfrom the FDA for this indication.³Now, Karypharm Therapeutics also plans to submit a marketing authorization application to the European Medicines Agency in 2020 in addition to the NDA.

Selinexor, a selective inhibitor of nuclear export, in combination with bortezomib (Velcade) and low-dose dexamethasone, has FDA approval for the treatment of patients with relapsed or refractory multiple myeloma. Selinexor is also being tested in the SIENDO study, in combination with placebo to treat patients with endometrial cancer.

The phase IIb SADAL study has met its target enrollment and continues with a goal completion date of December 2020.

References

1. Karyopharm Submits New Drug Application to U.S. FDA for Xpovio (selinexor) as a Treatment for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma [news release]. Newton, Massachusetts: Karyopharm Therapeutics Inc.; December 23, 2019. https://bit.ly/2sZr4aF. Accessed December 23, 2019.
2. Karyopharm Reports Positive Top-Line Phase 2b SADAL Data for Selinexor in Patients with Diffuse Large B-Cell Lymphoma at the American Society of Hematology 2018 Annual Meeting [press release]. Newton, Massachusetts: Karyopharm Therapeutics Inc.; December 1, 2018. https://bit.ly/2POvxWI. Accessed December 23, 2019.
3. Karyopharm. Karyopharm